This application requests funding for an 800 MHz nuclear magnetic resonance (NMR) spectrometer dedicated for life science research in the Upstate New York area. The proposed instrument will support the research programs of 9 NIH funded major users (holding a total of 11 NIH research grants in support of the described projects) as well as 7 significant minor users (holding a total of 7 grants from the NIH and other federal agencies). The group of users includes researchers from SUNY Upstate Medical University, Syracuse University and SUNY ESF, all located in Syracuse, NY as well as researchers from Cornell University, Ithaca, NY, University of Rochester, Rochester, NY and the Hauptman Woodward Institute, Buffalo, NY. Research areas supported by the proposed instrument include, but are not limited to, protein and RNA structure, folding and interactions. The biomolecules studied in the user's laboratories are involved in a variety of processes relevant to human health and disease such as energy transduction, RNA structure and mRNA splicing, development of protein and RNA based biosensors, oncogenesis, neuronal function and neurodegeneration, endocrine and exocrine signaling, regulation of histone gene transcription, and membrane transport. There is currently no 800 MHz instrument near the participating institutions so that researchers with a need for very high field NMR applications have to bring or send samples to one of the national facilities such as NMRFAM in Madison, WI or the Pacific Northwest National Labs in Richland, WA. The relatively long turnaround times as well as the cost for traveling and the difficulties with shipping sensitive samples limit the efficiency of these offsite alternatives, creating an ever-greater need for a local facility with esy access. The instrument for which funding is requested is forefront both regarding sensitivity and spectral resolution, thus allowing the analysis of structure, dynamics and interactions of proteins and nucleic acids beyond a size range of what is currently possible with the available instrumentation. Funding is also requested for a 5 mm cryogenically cooled probe for ultimate sensitivity allowing the analysis of samples with low abundance or poor solubility. The requested instrument is equipped with four channels for conducting triple resonance experiments with simultaneous decoupling of deuterium for analyzing (partially) deuterated samples. The instrument will be housed in the existing NMR facility at SUNY College of Environmental Science and Forestry (SUNY ESF), where it will be managed and maintained by the facility manager, Mr. David Kiemle. Mr. Kiemle has managed the SUNY ESF NMR facility for the past 25 years and has extensive experience with NMR analysis of bio macromolecules as well as maintenance and repair of modern NMR spectrometers. Acquisition of an 800 MHz NMR spectrometer will provide the Upstate New York region with a state-of-the-art instrument that will accelerate NIH funded biomedical research in the areas of structural biology and drug design, research areas that are essential if we want to find ways to fight human disease on a molecular level.